N-(1,1-Dimethylethyl)benzenesulfonamide → N-(tert-Butyl)-2-(1-{[1-(4-chlorophenyl)cyclopropyl]carbonyl}-3-hydroxypyrrolidin-3-yl)benzenesulfonamide

HRID 557907Notes

Reaction equation

HRID 557907 reaction equation
[C:1]([NH:5][S:6]([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)(=[O:8])=[O:7])([CH3:4])([CH3:3])[CH3:2].C([Li])(C)(C)C.[Cl:20][C:21]1[CH:26]=[CH:25][C:24]([C:27]2([C:30]([N:32]3[CH2:36][CH2:35][C:34](=[O:37])[CH2:33]3)=[O:31])[CH2:29][CH2:28]2)=[CH:23][CH:22]=1>CCCCC.CCOCC>[C:1]([NH:5][S:6]([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[C:34]1([OH:37])[CH2:35][CH2:36][N:32]([C:30]([C:27]2([C:24]3[CH:23]=[CH:22][C:21]([Cl:20])=[CH:26][CH:25]=3)[CH2:29][CH2:28]2)=[O:31])[CH2:33]1)(=[O:8])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 3

HCID 314059N-(1,1-Dimethylethyl)benzenesulfonamideHCID 666616461-{[1-(4-Chlorophenyl)cyclopropyl]carbonyl}pyrrolidin-3-oneHCID 178418306HCID 178418306, compound

Product 1

HCID 11627061N-(tert-Butyl)-2-(1-{[1-(4-chlorophenyl)cyclopropyl]carbonyl}-3-hydroxypyrrolidin-3-yl)benzenesulfonamide

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolvent2×HCID 8003PentaneSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of N-(tert-butyl)benzenesulfonamide (569 mg, 0.00267 mol) in ether (10 mL, 0.1 mol) was added 1.7 M of tert-butyllithium in pentane (4.7 mL) under nitrogen at −78° C. The mixture was stirred at −78° C. for 15 minutes, then at 0° C. for 1 hour. The reaction mixture then was cooled down to −78° C. again and a solution of 1-{[1-(4-chlorophenyl)cyclopropyl]carbonyl}pyrrolidin-3-one (640 mg, 0.0024 mol) in ether was added. After stirring for 2 hours, the reaction mixture was quenched with saturated NH4Cl aqueous solution and then extracted with EtOAc. The combined organic layer was washed with brine, dried over MgSO4 and concentrated. The crude product was purified using Combiflash eluting with 30% AcOEt in hexanes to afford the desired product. LC/MS (M+H+) 478.0.

Workup

  1. waitat 0° C. for 1 hour
  2. temperatureThe reaction mixture then was cooled down to −78° C. again
  3. stirringAfter stirring for 2 hours
  4. customthe reaction mixture was quenched with saturated NH4Cl aqueous solution
  5. extractionextracted with EtOAc
  6. washThe combined organic layer was washed with brine
  7. dry with materialdried over MgSO4
  8. concentrationconcentrated
  9. customThe crude product was purified
  10. washeluting with 30% AcOEt in hexanes

Sources & evidence

ORD record
ord-b50110cc57dc4926a50212676eeb5fae
Source dataset
uspto-grants-2011_11
Patent number
US08058288B2

Reaction notes

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